PLAU在头颈部鳞状细胞癌中的过表达及其潜在预后价值。
Overexpressed PLAU and its potential prognostic value in head and neck squamous cell carcinoma.
作者信息
Li Zhexuan, Chen Changhan, Wang Juncheng, Wei Ming, Liu Guancheng, Qin Yuexiang, She Li, Liu Yong, Huang Donghai, Tian Yongquan, Zhu Gangcai, Zhang Xin
机构信息
Department of Otolaryngology-Head and Neck Surgery, The Xiangya Hospital, Central South University, Changsha, Hunan, China.
Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China.
出版信息
PeerJ. 2021 Jan 15;9:e10746. doi: 10.7717/peerj.10746. eCollection 2021.
BACKGROUND
Metastasis is a major event for survival and prognosis in patients with head and neck squamous cell carcinomas (HNSCC). A primary cause of metastasis is the proteolytic degradation of the extracellular matrix (ECM). The plasminogen activator urokinase (PLAU) is involved in the transformation of plasminogen to plasmin leading to hydrolyzation of ECM-related proteins. However, the role of PLAU expression in HNSCC is unclear and the worth being investigated.
METHODS
PLAU expression profiles and clinical parameters from multiple HNSCC datasets were used to investigate the relationship of PLAU expression and HNSCC survival. GO and PPI network were established on PLAU-related downstream molecular. The stroma score was deconvoluted for analysis of PLAU's association with the immune environment. ROC analysis was applied to show the performance of PLAU in predicting HNSCC prognosis.
RESULTS
PLAU mRNA was significantly elevated, as opposed to its methylation, in HNSCC tumor samples over normal specimens (all < 0.01). Univariate and multivariate cox analysis showed PLAU could be an independent indicator for HNSCC prognosis. Combining with neck lymph node status, the AUC of PLAU in predicting 5-years overall survival reached to 0.862. GO enrichment analysis showed the major biological process (extracellular matrix organization and the P13K-Akt signaling pathway) may involve to the possible mechanism of PLAU's function on HNSCC prognosis. Furthermore, PLAU expression was positively correlated with stroma cell score, M1 type macrophages, and negatively associated with CD4 + T cell, Tregs cell, and follicular helper T cell.
CONCLUSIONS
PLAU might be an independent biomarker for predicting outcomes of HNSCC patients. The elevated expression of PLAU was associated with HPV positivity and neck node status. The PI3K-Akt pathway and aberrant proportions of immune cells might underly the mechanism of PLAU's oncogene role in HNSCC.
背景
转移是头颈部鳞状细胞癌（HNSCC）患者生存和预后的主要事件。转移的一个主要原因是细胞外基质（ECM）的蛋白水解降解。纤溶酶原激活物尿激酶（PLAU）参与纤溶酶原向纤溶酶的转化，导致ECM相关蛋白的水解。然而，PLAU表达在HNSCC中的作用尚不清楚，值得研究。
方法
使用来自多个HNSCC数据集的PLAU表达谱和临床参数来研究PLAU表达与HNSCC生存的关系。基于PLAU相关的下游分子建立基因本体（GO）和蛋白质-蛋白质相互作用（PPI）网络。对基质评分进行反卷积分析，以分析PLAU与免疫环境的关联。应用受试者工作特征（ROC）分析来显示PLAU在预测HNSCC预后方面的性能。
结果
与正常标本相比，HNSCC肿瘤样本中的PLAU mRNA显著升高，而其甲基化水平则相反（所有P<0.01）。单因素和多因素cox分析表明，PLAU可能是HNSCC预后的独立指标。结合颈部淋巴结状态，PLAU预测5年总生存率的曲线下面积（AUC）达到0.862。GO富集分析表明，主要生物学过程（细胞外基质组织和PI3K-Akt信号通路）可能涉及PLAU对HNSCC预后发挥作用的潜在机制。此外，PLAU表达与基质细胞评分、M1型巨噬细胞呈正相关，与CD4+T细胞、调节性T细胞（Tregs）和滤泡辅助性T细胞呈负相关。
结论
PLAU可能是预测HNSCC患者预后的独立生物标志物。PLAU表达升高与HPV阳性和颈部淋巴结状态有关。PI3K-Akt通路和免疫细胞比例异常可能是PLAU在HNSCC中发挥癌基因作用的机制基础。
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